Cobalamin-independent methionine synthase

Zinc is the active metal in the largest group of metalloproteins found in the nature. Recently a new class of zinc enzymes with a sulfur-rich environment has emerged the thiolate-alkylating enzimes, the most prominent of which is the cobalamine-independent methionine synthase.126 For these reasons several monothiolate zinc complexes have been prepared for the modelling of these enzymes with different N2S as (13),127 130 N20,13° 132 N3,132,133 S3,134 tripod ligands, or with Cd because of the favourable spectroscopic properties with an S3 tripod ligand.135... 

Taurog RE, Matthews RG. Activation of methyltetrahydrofolate by cobalamin-independent methionine synthase. Biochemistry 2006 45 5092-5102. 

ZnX(S2fV—donor)] (X = Br, CH3, SPh) species were prepared using the new mixed-donor ligands, ]Ph(pz)BtBu] and Ph(pztBu)BtBu. Protonolysis of [Zn(Me) Ph(pztBu)BttBu]] by PhSH in toluene yielded Zn(SPh) Ph(pz,Bu)BttBu, a synthetic analog of the homocysteine ligated form of cobalamin-independent methionine synthase.6... 

Two families of Met synthetases have been described so far, the cobalamin-dependent methionine synthetase (MetH) [30], and cobalamin-independent methionine synthase (MetE) [31], While Escherichia coU and many other prokaryotes express both enzymes, mammals use only the cobalamin-dependent methionine synthetase. Plants and yeasts only utilize the cobalamin-independent enzyme. In both cases, the Met 7 derives from homocysteine 8. 

Pejchal, R. and Ludwig, M.L. (2005) Cobalamin-independent methionine synthase (MetE) a face-to-face double barrel that evolved by gene duplication. PLoS Biol, 3, 254-265. 

It is interesting that E. coli contains two genes that code for methionine synthase metH for the cobalamin-dependent enzyme and metE for a cobalamin-independent enzyme that depends on an active site Zn + to stabilize deprotonated homocysteine (24). This thiolate species demethylates A -methyl-tetrahydrofolate, which is activated by proton transfer to N-5. MetE is less active ( 100 x ) than MetH, and so in the absence of Bi2 E. coli it produces much more MetE to compensate for the lack of MetH. 

There are two classes of methionine synthases, the cobalamin-dependent and cobalamin-independent enzymes. Both synthases catalyze the same reaction, Equation (20), the methylation of (5)-homocysteine (homocysteine) by -methyltetrahydrofolate (methyltetrahydrofolate). 

Figure 29.6 Pathways for the metabolism of homocysteine. Normal transsulfuration requires cystathionine P-synthase with vitamin Bg as cofactor. Reme-thylation requires 5,10-methylenetetrahydrofolate reductase and methionine synthase. The latter requires folate as cosubstrate and vitamin Bi2 (cobalamin) as cofactor. An alternative remethylation pathway also exists using the cobalamin independent betaine-homocysteine methyltransferase (Robinson 2000).

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